ARM A: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36;
bevacizumab IV over 30-90 minutes on days 1*, 15, and 29 OR on days 1 and 22; and irinotecan
IV over 30-90 minutes (at the same dose and schedule that the patient previously received)
beginning on day 1.

ARM B: Patients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days
1*, 15, and 29.

NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1
of subsequent courses.

In both arms, courses repeat every 6 weeks in the absence of disease progression or
unacceptable toxicity.

Patients are followed for 3 years.

Inclusion Criteria:

- Histologically or cytologically confirmed colorectal cancer

- Metastatic disease by diagnostic imaging studies

- Measurable disease

- At least 1 unidimensionally measurable lesion with minimum lesion size at least
twice the slice thickness of the imaging study used

- Refractory to irinotecan, evidenced by clinical documentation

- Received at least 1 prior irinotecan-containing chemotherapy regimen for
metastatic disease and progressed during or within 6 weeks after completion of
therapy

- Must have received prior irinotecan according to 1 of the following schedules:

- Weekly administration with a starting dose of 100-125 mg/m^2

- Biweekly administration (every other week) with a starting dose of approximately
180 mg/m^2

- Once every three weekly administration with a starting dose of 300-350 mg/m^2

- No known brain metastases

- No prior primary CNS tumors

- Performance status - ECOG 0-1

- Performance status - Karnofsky 80-100%

- More than 3 months

- WBC >= 3,000/mm^3

- Absolute neutrophil count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9 g/dL

- No bleeding diathesis or coagulopathy

- Bilirubin normal

- AST and ALT =< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of
known liver metastases)

- INR < 1.5 (for patients receiving warfarin)

- Creatinine =< ULN

- Creatinine clearance ≥ 60 mL/min

- No proteinuria

- No prior stroke

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No uncontrolled hypertension

- No clinically significant cardiac arrhythmia

- None of the following arterial thromboembolic events within the past 6 months:

- Myocardial infarction

- Cerebrovascular accident

- Transient ischemic attack

- Unstable angina

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 3 months
after study participation

- No significant traumatic injury within the past 28 days

- No grade 3 or greater neurotoxicity

- No uncontrolled seizures

- No prior allergic reactions attributed to compounds of similar chemical or biological
composition to study agents

- No prior irinotecan intolerance

- No ongoing or active infection requiring parenteral antibiotics

- No serious nonhealing active wound, ulcer, or bone fracture

- No psychiatric illness or social situation that would preclude study compliance

- No other concurrent uncontrolled illness that would preclude study participation

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No prior cetuximab

- No other prior epidermal growth factor receptor-directed therapy

- No prior anticancer murine or chimeric monoclonal antibody therapy

- Prior humanized monoclonal antibody therapy allowed

- No prior bevacizumab

- No other prior vascular endothelial growth factor-targeted therapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- More than 4 weeks since prior radiotherapy

- More than 28 days since prior major surgical procedure or open biopsy

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